Long-term measles antibody profiles following different vaccine schedules in China, a longitudinal study

Characterizing the long-term kinetics of maternally derived and vaccine-induced measles immunity is critical for informing measles immunization strategies moving forward. Based on two prospective cohorts of children in China, we estimate that maternally derived immunity against measles persists for 2.4 months. Following two-dose series of measles-containing vaccine (MCV) at 8 and 18 months of age, the immune protection against measles is not lifelong, and antibody concentrations are extrapolated to fall below the protective threshold of 200 mIU/ml at 14.3 years. A catch-up MCV dose in addition to the routine doses between 8 months and 5 years reduce the cumulative incidence of seroreversion by 79.3–88.7% by the age of 6 years. Our findings also support a good immune response after the first MCV vaccination at 8 months. These findings, coupled with the effectiveness of a catch-up dose in addition to the routine doses, could be instrumental to relevant stakeholders when planning routine immunization schedules and supplemental immunization activities.


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Data analysis
All analyses were performed in R version 4.1.0. The R code to replicate the analyses is available on GitHub at https://github.com/Sueleaf/ antibody-dynamics-against-measles.
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March 2021

Human research participants
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Reporting on sex and gender
All child participants were defined by sex. Relevant data are available within the paper and, in more detail, in the appendix file.

Recruitment
We used archived serum samples from two community-based longitudinal cohorts, including a cohort of mother-neonate pairs (n=1,066) and a cohort of children aged 1-9 years (n=4,188), that aimed to investigate the sero-epidemiological characteristics of paediatric enterovirus A71 infections in Hunan Province, China between September 2013 and September 2018.
A total of 1,066 pairs of neonates and mothers (from 1,054 mothers) were enrolled by well-trained nurses in the six local hospitals in Anhua County. We compared the characteristics of enrolled neonates with those from the same region who did not participate. Among neonates, sex and birthweight were similar. A total of 4,188 children aged 1-9 years were randomly enrolled by well-trained project personnel and/or village doctors in the three townships in Anhua County. Children were eligible for inclusion if they were 1-9 years of age at enrolment and resided in the study sites in the last ≥3 months. Within each township, simple random sampling was used for the selection of children aged 1-9 years. The randomization procedure could have furthest reduced the risk of self-selection bias.

Ethics oversight
This study was approved by the Institutional review board from WHO Western Pacific Regional Office (2013.10.CHN.2.ESR), the Chinese Centre for Disease Control and Prevention (201224), and Fudan University (2019-05-0756), and written informed consent was obtained from all caregivers of participants.
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Sample size
Only a subsample of the original cohorts was included in this study. In particular, we tested 2,629 participants' serum samples for measlesspecific IgG antibody; the included sera came from 555 mother-neonate pairs and 2,074 children aged between 1 and 9 years.
Data exclusions Child participants were excluded from analysis only if they failed to receive 2 doses of measles vaccine at ages consistent with the recommendation of China's national immunization program.

Replication
Reported results were consistently in replicated Elisa assays with replicates generating similar results. A subset of 120 serum specimens were performed in two independent assays: plaque reduction neutralization test (PRNT) and Elisa assay. We conducted the PRNT assay in biological duplicated wells in each dilution per samples. All replications were successful and gave similar results. Data were collected and checked by two of the authors. The statistical analyses were conducted and rechecked by two of the authors. Randomization 2,629 child participants were randomly selected from original cohorts.

Blinding
Blinding during serum sample collection was not needed because conditions were well controlled. There is only a unique number on the serum sample tube, and the identification information of the participant was blinded to experimental operator. Only anonymised data were used in the analysis.

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Validation
To evaluate the consistency between antibody concentrations measured through ELISA assay and the "gold standard" plaque reduction neutralization test (PRNT), a subset of 120 serum samples (including positive, equivocal, and negative IgG ELISA results) were re-evaluated using PRNT.

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Cell line source(s) Cell line used in this study were obtained from ATCC (Vero, Cat. #CCL 81)

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The cell line used were not authenticated

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Cell line was not tested for mycoplasma contamination Commonly misidentified lines (See ICLAC register) No commonly misidentified cell lines were used in the study